Dolabella auricularia synthesis

The antineoplastic, cyclic peptide dolastatin 3 (197) was isolated from the sea hare Dolabella auricularia in small quantities [187]. It bears much structural resemblance to the cyclic peptides of tunicates. Synthetic attempts indicated that the original published structure was incorrect [188]. Three reports of research directed towards synthesis of possible components of dolastatin 3 (197) failed to help with the correct structure [189-191]. Reisolation of 197 allowed the determination of the correct sequence of amino acids in this cyclic pentapeptide and the new structure was confirmed by synthesis [192]. Synthesis of dolastatin 3 (197) and the corresponding 12R diastereoisomer permitted study of the solution... 

The sea hare Dolabella auricularia has been the source of the powerful cytotastic and antineoplastic constituents designated as dolastatins [311]. Some of these compounds are thiazole-containing cyclic peptides. They were found in very small quantities in the animal (ca. 1 mg each from 100 Kg), making the isolation and structural elucidation of these peptides exceptionally challenging. A review on the dolastatins, written by G. R. Pettit in 1997, covers the reported literature regarding their isolation, characterization, biological activity, and synthesis [312]. Pettit and coworkers reported the thiazole-containing dolastatins dolastatin 3 (404) [313], 10 (2) [314], and 18 (407) [315]. The most important dolastatin and the most potent antineoplastic and tubulin-inhibitory substance known to date is the unique linear pentapeptide dolastatin 10 (2). 

The sea hare Dolabella auricularia has furnished aurilol (628), which is cytotoxic (728) and for which the structure has now been fully assigned by total synthesis (729). The Indian Ocean red alga Chondria armata, a member of the Laurencia family, contains armatols A-F (629-634) (730). 

Sone H, Kondo T, Kiryu M, Ishiwata H, Ojika M, Yamada K (1995) Dolabellin, a Cytotoxic Bisthiazole Metabolite from the Sea Hare Dolabella auricularia Structural Determination and Synthesis. J Org Chem 60 4774... 

Paterson I, Findlay AD, Florence GJ (2007) Total Synthesis and Stereochemical Reassignment of (+)-Dolastatin 19, a Cytotoxic Marine Macrolide Isolated from Dolabella auricularia. Tetrahedron 63 5806... 

The sea hare Dolabella auricularia was recorded to exhibit exceptionally potent biological properties, which were known to certain ancient Greeks and Romans. The most important antineoplastic constituent of D. auricularia was dolastatin 10 (362) (283), a linear pentapeptide that was reported to be the most potent antineoplastic substance known to date. The absolute configuration of362 was ascertained by total synthesis (284). Synthetic studies revealed that the initial structure (285) proposed for dolastatin 3 was incorrect (286-291). The structure of dolastatin 3 was reassigned as 363, and its absolute chirality was established by synthesis (292). The minimum energy conformation of 363 in solution was estab-... 

Sone, H., Nemoto, T., Ishiwata, H., et al. 1993. Isolation, structure, and synthesis of dolastatin D, a cytotoxic cyclic depsipeptide from the sea gare Dolabella auricularia. Tetrahedron Letters, 34 8449-52. 

Sone, H., Kondo, X, Kiryu, M., Ishiwata, H., Ojika, M., and Yamada, K. (1995). Dolabellin, a cytotoxic bisthiazole metabolite from the sea hare Dolabella auricularia Structural determination and synthesis. J. Org. Chem. 60, 4774-4781. 

Dolastatin 10 is a natural, cytotoxic antimitotic peptide with microtubule-inhibitory and apoptotic effects, isolated from the sea hare Dolabella auricularia. It has demonstrated in vitro and in vivo efficacy in the DU-145 human prostate cancer model. " Ratoveloma-nana-Vidal and Genet and co-workers proposed a total synthesis of dolastatin 10, where the three stereogenic centers were created by Ru(II)-catalyzed asymmetric hydrogenations of p-keto esters The reduction of P-keto ester 121 was accomplished with in situ generated [RuBr2(5)-SYNPHOS)] (1 mol%) as a catalyst under 12 bar hydrogen and at 50°C in EtOH. After 24 hours, it was achieved with complete conversion and good diastereoselectivity (3R) (3S) = 98 2. 

Paterson, I., Findlay, A.D., and Florence, G.J. (2007) Total synthesis and stereochemical reassignment of (+)-dolastatin 19, a cytotoxic marine macrohde isolated from Dolabella auricularia. Tetrahedron, 63, 5806-5819. 

Suenaga, K Mutou, T, Shibata, T, Itoh, T, Fujita, T, Takada, N., Hayamizu, H., Takagi, M., Irifime, T, Kigoshi, H and Yamada, K. (2004) Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia isolation, structure determination, synthesis, and biological activity. Tetrahedron, 60, 8509-8527. 

Kigoshi, H., Itoh, T., Ogawa, T., Ochi, K., Okada, M., Suenaga, K., and Yamada, K (2001) Auriculol, a cytotoxic oxygenated squalene from die Japanese sea hare Dolabella auricularia isolation, stereostructure, and synthesis. Tetrahedron Lett., 42, 7461-7464. 

Sone, H, Nemoto, T Ojika, M and Yamada, K. (1993) Isolation, stmcture, and synthesis of dolastatin C, a new depsipeptide from the sea hare Dolabella auricularia. Tetrahedron Lett., 34, 8445-8448. 

Kigoshi, H. and Yamada, S. (1999) Synthesis of dolastatin I, a cytotoxic cyclic hexapeptide from the sea hare Dolabella auricularia. Tetrahedron, 55,12301-12308. 

Ishiwata, H., Sone, H Kigoshi, H and Yamada, K. (1994) Total synthesis of doliculide, a potent cytotoxic cyclodepsipeptide from the Japanese sea hare Dolabella auricularia.], Org. Chem., 59, 4712-4713. 

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